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A non-profit publication of the Office of the University Relations of Virginia Tech,
including The Conductor, a special section of the Spectrum printed 4 times a year

Nagarkatti earns NIH award for cancer-research achievements

By Jeffrey S. Douglas

Spectrum Volume 19 Issue 30 - May 1, 1997

An Independent Scientist Award from the National Institutes of Health will
enable an investigator in the Virginia-Maryland Regional College of Veterinary
Medicine to intensify research that has already been credited with several
major victories in the battle against cancer.

Mitzi Nagarkatti, an associate professor in the college's Department of
Biomedical Sciences and Pathobiology who is exploring the role the immune
system plays in oncogenesis, was awarded a five-year $330,000 grant on the
basis of her laboratory's past research achievements and the promise it holds
for the future.

"There is so much being done in cancer research," said Nagarkatti, who will be
able to devote more time to her research as a result of the grant. "But there
is so much more to do, and much of this must be done in the field of
immunotherapy."

Immunotherapy shows great promise in the war against cancer because it does
not involve the generalized cellular destruction associated with conventional
chemotherapy, there is no "resistance" developed to the pharmacologic agents,
and it is highly specific for the targeted tumor cells.

Immunotherapy has already led to successful new approaches for melanoma and
renal-cell carcinoma, Nagarkatti said, and work is under way around the nation
which should lead to other important applications in the future. But much
remains to be learned about how the body's immune system can be stimulated to
contain and destroy cancer cells.

Nagarkatti's pioneering work has examined the role T cells play in the
destruction of tumors. While scientists had understood that T-cells used T-cell
receptor molecules as part of the process of destroying tumors, Nagarkatti's
research demonstrated an alternative mechanism for this process in 1991.

In research published in the Proceedings of the National Academy of Science,
Nagarkatti discovered that T cells also use another adhesion molecule called
CD44 in the process of attacking cancer cells. Several laboratories around the
world have subsequently reported similar findings with other immune cells that
kill cancer.

This discovery proved of major significance. Not only did it provide
immunotherapists with another protocol for activating T-cells to destroy
non-specific tumor targets, it provided information that would prove critical
in scientific efforts to understand a troublesome medical problem called
vascular-leak syndrome.

In results published in the International Journal of Cancer in 1995,
Nagarkatti presented work which suggested that under certain conditions,
vascular-leak syndrome could be caused when T-cells bearing the CD44 adhesion
molecule destroyed the endothelial cells lining blood-vessel walls.

Nagarkatti and colleagues were looking at ways to mitigate this endothelial
cell damage by activating cytotoxic T-cells to up-regulate the CD44 adhesion
molecules when they made an astonishing discovery: T-cell lines they had
cultured became cancerous.

In a breakthrough which has provided a critically important opportunity to
understand how cancer originates, Nagarkatti and her colleagues discovered that
the T-cells were producing and responding to their own growth factor, called
interleukin-2. This mechanism, termed autocrine growth, was the first
demonstration that cancer can occur outside of a living organism.

Published in the Proceedings of the National Academy of Sciences in 1994, this
work sounded a major note of caution in clinical care and provided significant
new hope for treating cancer.

"First, it suggested that extreme caution should be used when using cultured T
cells to treat cancer or viral infections to make sure that such cells do not
contain `transformed' or cancer cells," Nagarkatti said. "Second, it showed
that T-cell leukemias and lymphomas that originate using autocrine growth
mechanisms can be treated using antagonists against growth factors such as
interleukin-2."

Subsequent work in her laboratory has demonstrated that complete tumor
regression has occurred when tumor-bearing mice are treated with antibodies
against interleukin-2 or its receptor.

"Independent Scientist Awards have always been prestigious awards that are
very difficult to obtain," said Lud Eng, head of the college's Department of
Biomedical Sciences and Pathobiology. "We are very pleased to see Dr.
Nagarkatti's success in earning the award, and we are very excited about the
work she is doing in her laboratory."

Nagarkatti, who has received about $1.7 million in funding from the National
Institutes of Health and the American Cancer Society throughout her career,
accepted a post in Virginia Tech's Department of Biology in 1986 after
conducting NIH-funded post-doctoral work with noted immunologist Alan Kaplan at
the University of Kentucky.

She has conducted much of her work in collaboration with her husband Prakash,
an associate professor biology in the university's biology department, and with
researchers in the VMRCVM, where she accepted a post in 1994.

Nagarkatti has published more 60 professional papers, and organized the Annual
Seminar of Cancer Researchers in Virginia at Virginia Tech in 1994.